Optiquel as Corticosteroid-sparing Therapy for Chronic Noninfectious Uveitis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )
ClinicalTrials.gov Identifier:
NCT01195948
First received: September 3, 2010
Last updated: February 28, 2014
Last verified: February 2014
  Purpose

Background:

  • Uveitis is a serious inflammatory condition in which the body's immune system attacks parts of the eye, often causing vision loss. Uveitis treatments involve various drugs that suppress the immune system, but these medicines sometimes do not work or may cause serious side effects. Researchers are interested in developing new treatments for uveitis that are more effective and have fewer side effects.
  • Optiquel is a natural product. It is an experimental medication being tested for its effectiveness again uveitis. It contains B27PD, a small protein fragment, which is similar to proteins in the parts of the eye being attacked by the immune system. Taking B27PD by mouth may induce oral tolerance, in which the immune system is taught to recognize and not attack normal parts of the human body.

Objectives:

- To evaluate the safety and effectiveness of B27PD (Optiquel ) as a treatment for uveitis.

Eligibility:

- Individuals at least 18 years of age who have had noninfectious uveitis in one or both eyes for at least 3 months, have vision of 20/200 or better in at least one eye, and are taking daily prednisone or an equivalent medication.

Design:

  • Participants will be screened with a physical examination, medical history, blood and urine tests, and an eye exam.
  • This study will last 52 weeks, with at least 17 study visits.
  • Participants will be divided into three groups, and will randomly be selected to receive one of two different doses of B27PD or a placebo. During the study, participants will also have their dose of prednisone or other steroid medication reduced.
  • Participants will take one pill three times per week on Monday, Wednesday, and Friday, for a total of 26 weeks. The pill should be taken in the morning (at least 4 hours after eating and at least 30 minutes before eating). Participants may take the pill with water, but should not consume any other beverages or any kind of food until at least 30 minutes have passed to prevent stomach upset. The pills should be stored in the refrigerator.
  • During the first 12 weeks of the study, participants will have a study visit every 2 weeks. For the remainder of the study, participants will have a study visit every 4 weeks. Participants will have frequent blood and urine tests, and will also have eye examinations and special procedures (fluorescein angiography and indocyanine green angiography) to evaluate the effectiveness of the treatment.

Condition Intervention Phase
Uveitis
Drug: Peptide B27PD
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Peptide B27PD (Optiquel ) as Corticosteroid-sparing Therapy for Chronic Non-infectious Uveitis (BOOTS)

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • The objective of the proposed study is to evaluate the safety and efficacy of Optiquel as a corticosteroid-sparing agent for chronic non-infectious uveitis in participants receiving oral corticosteroid therapy alone or with an anti-metabolite... [ Time Frame: Time from randomization to recurrence, loss to follow-up, or end of study ]

Secondary Outcome Measures:
  • Proportion of participants determine to be a Treatment Failure, defined as recurrent (or flare) of uveitis, defined as at least a 2-step increase in anterior chamber cells and/or vitreous haze (using SUN grading system) or a drop in visual acuit...
  • Reduction in exposure to corticosteroid as measured by the area under the dose-time curve.
  • Changes in best-corrected visual acuity (BCVA).
  • Changes in fundus autofluorescence.
  • Changes in HS-ICG.

Enrollment: 31
Study Start Date: August 2010
Study Completion Date: February 2014
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Peptide B27PD
    N/A
Detailed Description:

Objective: The objective of this study is to evaluate the safety and efficacy of the peptide B27PD (Optiquel ) as a corticosteroid-sparing agent for chronic non-infectious uveitis in participants receiving oral corticosteroid therapy alone or combined with an immunosuppressive agent in a proof-of-concept clinical trial.

Study Population: Eligible patients with non-infectious uveitis requiring at least 20 mg but no more than 40 mg of oral prednisone, or equipotent dose of alternative corticosteroid medication to maintain a quiescent eye, will be eligible.

Design: In this single center, Phase I/II, double-masked, randomized, placebo-controlled, parallel group treatment study, the safety and efficacy of the peptide B27PD will be investigated in 60 participants with non-infectious uveitis. Initially, 60 participants were to be enrolled; however, due to lack of efficacy, only 31 participants were enrolled. Eligible participants were to be be randomized to one of three treatment groups: 1 mg B27PD, 4 mg B27PD or placebo, to be taken three times per week for 24 weeks. All remaining participants will be followed through a common termination date. The common termination date will be established once the last enrolled participant reaches his/her Week 28 visit (four weeks following his/her last investigational treatment).The time to recurrence of uveitis in either eye occurring in the 52 weeks following the initial dosing will be evaluated in each treatment group. Recurrence will be defined as an increase in anterior chamber cells and/or vitreous haze of at least 2 steps (using the SUN grading system). Ophthalmic examinations to assess the uveitis will include visual acuity, intraocular pressure (IOP), slit lamp biomicroscopy, ophthalmoscopy, optical coherence tomography (OCT) and fluorescein angiography.

Outcome Measures: The primary outcome variable is the time to recurrence of uveitis activity in participants of each treatment group, during or after tapering of oral prednisone to a dose of 7.5 mg/day, or equipotent dose of alternative corticosteroid medication. Secondary efficacy outcome variables include the proportion of participants determined to be a Treatment Failure, defined as recurrence (or flare) of uveitis (at least a 2-step increase using the SUN grading system) or a drop in visual acuity of greater than or equal to 15 ETDRS letters at 24 and 52 weeks. Other secondary efficacy outcomes include the reduction in exposure to corticosteroid as measured by the area under the dose-time curve, and changes in best-corrected visual acuity (BCVA) fluorescein angiography, fundus autofluorescence and high-speed indocyanine green angiography (HS-ICG). Ocular safety measurements include intraocular pressure (IOP) and optical coherence tomography (OCT) for confirmation of suspected macular edema. Systemic safety variables include adverse events, clinical blood chemistry and hematology, urinalysis, vital signs, weight and medical evaluation at baseline and at the end of the study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Participants will be selected, according to the inclusion criteria listed below:
  • Participant must be 18 years of age or older.
  • Participant must be able to understand the informed consent process and sign the informed consent form.
  • Participant has been diagnosed with non-infectious unilateral or bilateral uveitis for at least three months. Participants who were diagnosed more than a year prior to enrollment must have had a recurrence in ocular inflammation within the past year.
  • Participant must be receiving a current treatment with prednisone between 20 to 40 mg/day (or an equipotent dose of an alternative corticosteroid). Participants who are on a regimen of no more than one anti-metabolite inhibitor at the time of randomization (e.g., azathioprine, methotrexate, mycophenolate) in addition to the prednisone may be enrolled and are allowed to continue the anti-metabolite.
  • The participant s uveitis must be controlled in eligible eyes, quiescent eyes (anterior chamber cells and vitreous haze SUN grade of 0).
  • The participant s eligible eye(s) is able to be evaluated for activity of disease both biomicroscopically and ophthalmoscopically.
  • The participant s baseline intraocular pressure must be greater than 5 mmHg and less than or equal to 30 mmHg in both eyes. Concurrent use of intraocular pressure-lowering medication and/or prior glaucoma surgery is acceptable.
  • Participant has best-corrected distance visual acuity in the better seeing eye of 20/200 or better (greater than or equal to 34 ETDRS letters).
  • Female participants of childbearing potential must not be pregnant or lactating and must be willing to undergo serum pregnancy tests throughout the study.
  • Women of childbearing potential must agree to use reliable methods of contraception while receiving the study medication and for 6 weeks following the last administration. Acceptable methods of contraception include hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring), intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom with spermicide) or surgical sterilization (hysterectomy, tubal ligation or partner with vasectomy).

EXCLUSION CRITERIA:

Participants who meet one or more of the following criteria are not eligible for study participation:

  • Participant has a non-iatrogenic immunodeficiency state (e.g., HIV infection or congenital immunodeficiency).
  • Participant had intra-ocular surgery or intraocular injection within three months prior to randomization.
  • Participant is expected to have an elective ocular surgery or intraocular injection during the study period.
  • Participant is using systemic corticosteroid therapy for a non-ocular disease or non-ocular organ involvement.
  • Participant has a history or diagnosis of Behcet s disease.
  • Participant has a clinically suspected, and/or confirmed central nervous system or ocular lymphoma.
  • Participant has an active systemic infectious disease or malignancy that requires treatment.
  • Participant has a known chronic disease or condition of the gastrointestinal system that may interfere wih the absorption of the investigational product as determined by the investigator (e.g., active hepatitis, chronic diarrhea, inflammatory bowel disease, Crohn s disease, ulcerative colitis, celiac disease, diverticulosis or diverticulitis).
  • Participant has two or more food allergies.
  • Participant has an implant containing anti-inflammatory, immunosuppressive or antiviral drugs, unless a period 50% longer than the anticipated duration of effect of the implant has elapsed.
  • Participant received periocular corticosteroid injections within 4 months prior to randomization or is expected to need periocular corticosteroid injections during the study duration.
  • Participant received treatment with infliximab, etanercept, adalimumab, interferon, cyclosporine, tacrolimus, sirolimus, within two weeks prior to randomization.
  • Participant received cytotoxic therapy (e.g., cyclophosphamide) within six months prior to randomization.
  • Participants for whom, in the physician's opinion, any of the protocol procedures may pose a special risk not outweighed by the potential benefits of participating in the study.
  • Participant who is unlikely to comply with the study protocol or who is likely to be moving or lost to follow-up.
  • Participant who is currently enrolled or has been participating in any other investigative therapeutic clinical trial during the three months prior to randomization.
  • Participant has a known need for a colonoscopy or surgery of the gastrointestinal tract during the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01195948

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Robert B Nussenblatt, M.D. National Eye Institute (NEI)
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )
ClinicalTrials.gov Identifier: NCT01195948     History of Changes
Other Study ID Numbers: 100191, 10-EI-0191
Study First Received: September 3, 2010
Last Updated: February 28, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Uveitis
Oral Tolerance

Additional relevant MeSH terms:
Uveitis
Chorioretinitis
Uveal Diseases
Eye Diseases
Retinitis
Retinal Diseases
Choroiditis
Choroid Diseases
Uveitis, Posterior
Panuveitis

ClinicalTrials.gov processed this record on October 19, 2014